These studies are designed to follow the development of adenomas and carcinoma in people with inherited predisposition to familial polyposis and the Gardner syndrome, to define indexes that represent phenotypic expressions of preneoplasia, and to predict carriers of the gene defect before clinical signs appear. During the initial phase of this project, members of three kindreds having varying degrees of expression of familial polyposis and the Gardner syndrome were studied. The subjects were examined and classified in categories including those having known Gardner syndrome with expression of polyposis and extracolonic manifestations (osteomas, fibromas, epidermoid cysts, desmoid neoplasms, odontomas, and supernumerary teeth); polyposis without extracolonic manifestations of disease; indeterminate Gardner syndrome with extracolonic manifestations but without polyposis; potential carriers of the gene defect known to be asymptomatic progeny of an affected parent; members of kindred branches that were polyposis and cancer free for three or more generations; additional control subjects. These characteristics were identified in members of familial aggregates. In addition, initial examination of biopsy specimens of colonic mucosa revealed the presence of chronic inflammatory disease consistent with ulcerative colitis in four siblings of a familial group. Multiple gastric polyps were present in two siblings, and duodenal adenomas were found in other subjects. Distal esophagitis was present in three subjects whose ages were 16-21 years with distal esophageal polyps present. Further measurements are now underway in the continued examination of these subjects, and intestinal, cutaneous, and blood specimens are being analyzed for measurement of growth charcteristics of cells, enzyme activities, and recognitive immunity. Patterns of inheritance of abnormal phenotypic attributes are being studied in symptomatic subjects, and in those who are potential carriers of the genetic defect leading to familial polyposis and Gardner syndrome.